The studies proposed in this renewal grant application exemplify a continuation of our ongoing work on the nature of retrovirus- related structures present in cell types previously purported to lack endogenous retroviruses. We have recently demonstrated that several species of avian cells previously thought to lack avian retrovirus-related sequences in fact contain such sequences in the form of two genetic structures. The structure of one group of viral-related genetic sequences exists as endogenous retroviruses, since they contain gag-, pol-, env and LTR-related sequences linked to one another in the form of a provirus. The structure of the other group of retrovirus-related genetic sequences exists as solo gag-, pol-, env-, and LTR-related sequences not linked to one another in the form of a provisus. In an effort to shed light on the nature of these novel families of avian endogenous retroviruses and the solo retrovirus-related genetic sequences present cell types, we plan to: 1) isolate and characterize both classes of avian retrovirus genetic sequences present in these cell types in order to delineate their precise nature; 2) identify and characterize the transcriptional related structures in other avian species as well as other vertebrate genera in an attempt to define the nature of more distantly-evolved sequences and novel classes of endogenous retroviruses. The methodologies that we plan to employ to achieve these objectives are, for the most part, already implemented in our laboratory and include a variety of physicochemical, enzymological, and hybridization techniques available for the analysis of DNA, RNA, and protein,